T1ρ mapping improvement using stretched-type adiabatic locking pulses for assessment of human liver function at 3T

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T1ρ mapping improvement using stretched‑type adiabatic locking pulses for assessment of human liver function at 3T

著者 奥秋 知幸

著者別表示 Okuaki Tomoyuki journal or

publication title

博士論文本文Full 学位授与番号 13301甲第4616号

学位名 博士(保健学)

学位授与年月日 2017‑09‑26

URL http://hdl.handle.net/2297/00050302

doi: 10.1016/j.mri.2017.03.006

Creative Commons : 表示 ‑ 非営利 ‑ 改変禁止 http://creativecommons.org/licenses/by‑nc‑nd/3.0/deed.ja

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T

1ρ

mapping improvement using stretched-type adiabatic locking pulses for assessment of human liver function at 3 T

Tomoyuki Okuaki

a,b,

⁎ , Yukihisa Takayama

c

, Akihiro Nishie

d

, Tetsuo Ogino

e

, Makoto Obara

e

, Hiroshi Honda

d

, Tosiaki Miyati

b

, Marc Van Cauteren

a

aPhilips Healthcare, Tokyo, Japan

bDivision of Health Science, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan

cDepartment of Radiology Informatics and Network, Kyushu University, Graduate School of Medical Sciences, Fukuoka, Japan

dDepartment of Clinical Radiology, Kyushu University, Graduate School of Medical Sciences, Fukuoka, Japan

ePhilips Electronics Japan, Tokyo, Japan

a b s t r a c t a r t i c l e i n f o

Article history:

Received 30 November 2016

Received in revised form 17 February 2017 Accepted 25 March 2017

Available online xxxx

Purpose:The purpose of this study is to investigate the performance of stretched-type adiabatic spin lock pulses for homogeneous spin locking with aflexible spin lock time (TSL) setting.

Methods:Tvalues were obtained from 61 patients andfive normal volunteers who were categorized using the Child–Pugh classification and scanned using each spin lock pulse type. The pulses used were the block and two kinds of hyperbolic secant (HS); HS8_10, and HS8_5. Visual scoring was categorized using a four point scale (1:Severe, 2:Moderate, 3:Mild and 4:None) to evaluate the homogeneity of the Tmap and the source images obtained by each spin lock pulse. Mean Tvalues among the patient groups with different Child–Pugh classifi- cation were compared.

Results:The visual assessment scores were 1.98 ± 1.05 for block pulse locking, 3.87 ± 0.39 for HS8_10 pulse locking, and 3.83 ± 0.45 for HS8_5 pulse locking, respectively. The scores between block pulse and HS8_10 were significantly different (pb0.001), as were those between block pulse and HS8_5 (pb0.001).

The median Tvalues of normal liver function, Child–Pugh A, and Child–Pugh B or C were 37.00 ms, 40.77 ms, and 42.20 ms for block pulse, 46.75 ms, 50.78 ms, and 55.60 ms for HS8_10, and 48.80 ms, 55.42 ms, and 57.80 ms for HS8_5, respectively.

Conclusion:The spin locking sequence using stretched-type adiabatic pulses provides homogeneous liver T maps with reduced artifact and is necessary for a robust evaluation of liver function using T.

© 2017 Elsevier Inc. All rights reserved.

Keywords:

T

stretch type adiabatic pulse liver

spin lock hyperbolic secant

1. Introduction

Assessment of liver function is essential for the management of pa- tients with liver disease and for the prevention of postoperative hepatic failure. Liver function is frequently estimated by measuring biochemical parameters in the blood, such as bilirubin, aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, albumin, and prothrombin activity[1]. The Child-Pugh classification[2,3]is based on a combination of serum albumin, serum bilirubin, prothrombin activity, ascites, and hepatic encephalopathy to reflect liver functional reserve more accu- rately than by using any of these biological factors alone[3]. Previous

reports using magnetic resonance imaging (MRI) state that T1 mapping and T2* mapping can be used to assess liver function[4,5]. Liverfibrosis is a common feature of most chronic liver diseases and ultimately pro- gresses to liver cirrhosis with the accumulation of proteoglycans and collagen and other macromolecules in the extracellular matrix[6–8].

Conventional MRI cannot evaluate liverfibrosis directly. Liver biopsy is carried out for the diagnosis and monitoring of progression as a stan- dard of reference; however, liver biopsy is an invasive procedure, is prone to error, and involves the risk of complications[9,10]. Another ap- proach, magnetic resonance elastography (MRE), is a noninvasive method for the detection offibrotic liver and staging of liverfibrosis [9–11]; however, additional equipment is required for MRE, especially the transducer to generate a vibrational wave[12].

Recently, Tmeasurement has been widely applied to investigate diseases of the cartilage[13–17], prostate, disc[18], myocardium[19], and liver[7,8,20–23]. With regard to the liver, Wang et al. reported that in an animal model Trelaxation was used successfully to detect early liverfibrosis and that increased liver collagen results in an increase Abbreviations:MRE, magnetic resonance elastography; RF, radio frequency; TSL, spin

lock time; HS, hyperbolic secant; MLEV, Malcolm H. Leviti; IDL, Interactive Data Language; ROI, region of interest.

Corresponding author at: Philips Healthcare , 13-37, Kohnan 2-chome, Minato-ku, Tokyo, 108-8507 Japan.

E-mail address:tomoyuki.okuaki@philips.com(T. Okuaki).

http://dx.doi.org/10.1016/j.mri.2017.03.006 0730-725X/© 2017 Elsevier Inc. All rights reserved.

Contents lists available atScienceDirect

Magnetic Resonance Imaging

j o u r n a l h o m e p a g e :w w w . m r i j o u r n a l . c o m

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of the Tvalue[20]. Contrary to that report, Sirlin et al. suggested that Trelaxation does not directly reflect liverfibrosis[8]. Moreover, Allkemper et al. and Rauscher et al. reported that Tvalues were prolonged proportional to the progression of the Child–Pugh grade and liver cirrhosis[24,25].

In most of these studies, a block pulse was used as a spin lock pulse.

However, at 3 T, severe artifacts due to B0 and B1 inhomogeneity were observed, especially for a larger organ like the liver. Furthermore, these artifacts not only cause artefactual Timages but also hamper accurate measurement of the T. Such artifacts are caused by inhomogeneous B0 and B1 and therefore imperfect excitation pulses in the spin lock pulse train. Witschey et al.[26]reported an improved spin locking pulse, namely the echo locking method, to remediate these artifacts in a phan- tom and the human brain but not in the liver.

Adiabatic pulses are characterized by the simultaneous modulation of radio frequency (RF) wave amplitude and frequency. Well-chosen modulation wave forms result in insensitivity to a broad range of B0 and B1 inhomogeneity[27–31].

A few papers reported application of adiabatic pulses for spin locking. Taheri S et al. and Michaeli S reported a simulation study[32, 33], Mangia S et al. studied the brain at 4 T[34], Casula V et al. studied knee cartilage[35]and Yang Q et al. applied them to liver[22].

The purpose of this study was to investigate the performance of the stretched-type adiabatic spin lock pulses for homogeneous spin locking with aflexible spin lock time (TSL) setting. Moreover, we aimed to in- vestigate the clinical usefulness of the Tvalue acquired using the im- proved spin locking pulses for the assessment of liver function.

2. Materials and methods 2.1. Subjects

This study was approved by our Institutional Review Board; it com- plied with the standards of the Ethics Committee.

Between June 2013 and July 2014, 69 patients underwent MRI of the liver, including Tmaps, because a liver tumor was suspected due to chronic liver disease or malignant disease in other organs. We excluded eight patients with difficulty to determine Child–Pugh classification. Of the remaining 61 patients, 51 patients were categorized as Child–Pugh A (age range, 40–83 years; mean age, 63.4 years) and 10 as Child– Pugh B or C (age range, 43–74 years; mean age, 61.3 years). As the con- trol, five normal volunteers (age range, 50–55 years; mean age, 52.6 years) were scanned.

2.2. Imaging protocols

MRI data acquisition was performed on a 3 T clinical scanner (Achieva TX; Philips Healthcare, Best, Netherlands). A 32-channel phased-array receiver coil was used.

Three types of rotary echo spin lock pulses were generated to achieve T-weighted images (Table 1). The non-selective block pulse was used as a conventional spin lock pulse (Fig. 1). The spin lock pulse amplitude was set at 500 Hz, following the literature[20,36]; the TSLs were 1, 20, and 40 ms. Two different types of spin lock pulses type

were used, namely the block pulse and the stretched-type adiabatic preparation pulses.

The hyperbolic secant (HS) pulse, known to be insensitive to varia- tions of B1 intensity approaching several orders of magnitude, was used as a base. The time variation of the wave form modulations was modified to further optimize the performance of the pulse.

An effective magneticfield (ωeff=γBeff) is induced by the pulse, whereBeffis the effective magneticfield vector andγis the gyromagnet- ic ratio. The time-dependent magnitude of the effectivefield is:

ωeffð Þ ¼t ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi ω21ð Þ þt ðω0−ωRFð Þt Þ2 q

where;

ω1(t) =ω1maxsech(βtn), (ω0−ωRF(t))= A∫sech2(βτn)dτ, whereω1max

is the maximum amplitude. A determines the frequency sweep amplitude and is equal toμβ.μis a dimensionless parameter andβis a modulation angular frequency.ω0is the on-resonance fre- quency equal toγB0andωRFis the frequency modulation. For the orig- inal HS pulse, n equal to 1, whereas the stretched adiabatic pulse is generated bynN1 (Fig. 2). We applied a high n factor (n= 8) to gener- ate two types of adiabatic spin locking pulse from the original pulse, which was characterized byμ= 5 andβ= 4 rad/s. The parameters of thefirst pulse type were pulse duration 10 ms, frequency sweep 636.6 Hz, and maximum amplitude 6.37μT (HS8_10). The second pulse type had a pulse duration 5 ms, frequency sweep 1273.2 Hz, and maximum amplitude 13.48μT (HS8_5). The Beffchange during the two types of adiabatic pulse is indicated inFig. 3; the average Befffield of HS8_10 and HS8_5 was 500 Hz and 1000 Hz, respectively. For these adiabatic pulses, the rotating frame relaxation time was measured using a pulse module consisting of consecutive identical HS pulses.

The number of pulses was increased to obtain the Timages with dif- ferent TSLs forfitting from two to four for HS8_10 and from four to eight for HS8_5, with MLEV phase cycling[37](Fig. 4). The TSL was set to 0, 20, and 40 ms by increasing the number of pulses. TSL = 0 rep- resents the absence of a spin lock pulse.

Table 1

Design parameters for the spin lock pulses.

Spin lock pulse Pulse type

Pulse duration per pulse

(ms) Frequency sweep (Hz)

Spin lock frequency (Hz)

B1max (μT)

TSL (ms)

Block Block 500 11.7 1,20,40

HS8_10 Stretched-type adiabatic (n= 8) 10 636.6 500.0* 6.73 0,20,40

HS8_5 Stretched-type adiabatic (n= 8) 5 1273.2 1000.0* 13.48 0,20,40

*average effective SL frequency.

Fig. 1.Scheme of the Tspin lock RF cluster using block pulse. The RF pulse train is 90(+x)SL(+y)SL(−y)90 (−x). Magnetization is nutated into thexaxis by the initial 90° pulse. The magnetization vector is then spin locked by two block pulses, lockingfirst along the +yand then the–yaxis. Finally, the magnetization is nutated back into thezaxis by the 90° pulse along the–xaxis.

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We simulated the efficiency of these three types of spin lock pulse in function of B0 and B1 using Bloch equations at TSL 20 ms (Fig. 5). The simulation was based on the Bloch-equations, solved using the ordinary differential equation function of Matlab (Mathworks, Natick, MA, USA).

We did not take relaxation effects into account. Thefigures show the final magnetization, in function of B0 and B1, after presenting each type of spin lock pulse combination to the equilibrium magnetization.

The spin locking block pulse combination nutates the equilibrium magnetization into the x axis by the initial 90° pulse and is then spin locked by two block pulses that have opposite phases. After the spin locking the magnetization is nutated back into the z axis by a−90°

pulse (Fig.5a).

For the two types of stretched-type adiabatic pulse, the magnetiza- tion is spin locked by an even number of adiabatic pulses (Fig, 5 b and c).

In case of perfect locking, and ignoring relaxation, thefinal magneti- zation is equal to the equilibrium magnetization.

In thefigures we show thefinal magnetization as a fraction of the equilibrium magnetization, in function of both B0 and B1.

For imaging, a three-dimensional turbofield echo sequence using the parallel imaging technique was employed with breath holding.

Volume shimming was used to minimize B0 inhomogeneity. Other im- aging parameters were as follows: repetition time 2.1 ms, echo time 0.98 ms,field of view 360 × 306 mm2, matrix 256 × 205, slice thickness 10 mm, slice gap 0 mm, number of slices 3, number of acquisitions 1, shot interval 5000 ms, and scan time of T-prepared image with each TSL 11.7 s. Scanned slices were set at the level of the hepatic hilum.

2.3. Timage analysis

Tmaps were generated on a pixel-by-pixel basis using in-house developed software program written in Interactive Data Language (IDL 6.3; ITT, Boulder, CO) using a mono-exponential decay model:

M(TSL) = M0 × exp.(−TSL/ T), where M0 and M(TSL) denote the equilibrium magnetization and Tspin lock prepared magnetization for each TSL, respectively. Tmaps were generated for each spin lock type with a Levenberg–Marquardtfitting algorithm[38]. For quantifica- tion of liver Tvalue, three regions of interest (ROIs) were manually placed on the liver parenchyma; the sizes of the ROIs were as large as possible, approximately 50–150 mm2, avoiding blood vessels, tumors, and artifacts.

2.4. Visual assessment

Evaluation of the homogeneity of the Tmaps and the Tsource images was scored through visual evaluation by two MR clinical scien- tists (T.O. and M.O.) with 10–16 years of experience. Visual scoring was categorized using a 4-point scale as 1 severe, 2 moderate, 3 mild, and 4 none. The definition of visual scoring was as follows:

1: Severe: Severe artifacts, difficult to evaluate Tvalues;

2: Moderate: Mildly severe artifacts. Artifacts should be avoided to measure the Tvalue, however, thefitting to calculate Tvalues is acceptable using a limited area;

3: Mild: Some artifacts on the image;

4: None: No artifacts on the image.

2.5. Statistical analysis

We employed the Tukey–Kramer method to compare visual scoring between the image qualities and the Friedman test to compare the mean Tvalues of each spin locking pulse (the block pulse, HS8_10, and HS8_5).

Mean Tvalues among the patient groups with different Child– Pugh classifications were compared using the Kruskal–Wallis test followed by Tukey's post hoc test. Statistical analysis was performed Fig. 2.Scheme of the amplitude and frequency modulation function for HS1 and HS8. HS8

is the stretched-type version of HS1. Time is shown on the horizontal axis.

Fig. 3.The amplitude, frequency and effective frequency change during two types of adiabatic pulses: HS8_10 a) and HS8_5 b).

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using EZR free software (Saitama Medical Center, Jichi Medical Univer- sity, Saitama, Japan)[39]. APvalueb0.01 was considered significant.

3. Results

The simulation suggested that the HS8_5 pulses would perform bet- ter as a locking pulse, given that for a broad range of B0 and B1 values the equilibrium magnetization is restored after the locking.

Two cases of typical source images and Tmaps are shown inFig. 6a and b. There were artifacts on most of the spin locking images using the block pulse; however, the artifact level on the source images and T mapping obtained with the adiabatic spin locking pulses was signifi- cantly reduced.

3.1. Visual assessment

The intraclass correlation coefficient of visual scoring between the two readers was 0.90, indicating good concordance in the readers' visual scoring.

The visual assessment score (mean ± standard deviation) of the ho- mogeneity of the Tmaps resulted in 1.98 ± 1.05 for block pulse locking, 3.87 ± 0.39 for HS8_10 pulse locking, and 3.83 ± 0.45 for HS8_5 pulse locking, respectively. Both types of adiabatic spin locking- derived maps scored significantly better than the block pulse locking- derived maps (Fig. 7). The visual assessment score showed significant differences between the block pulse and HS8_10 (Pb 0.001) and

between block pulse locking and HS8_5 (Pb0.001). There was no signif- icant difference between HS8_10 and HS8_5 (P= 0.792).

3.2. Tvalues

It was not possible to draw an ROI avoiding the artifacts in all source images for some Tmaps using block pulse because artifacts appeared in different locations in each source image. This resulted in a limited area where the Tvalue could be calculated to generate a reliable T map. In contrast, there were no severe artifacts in most of the source im- ages using adiabatic pulses.

The Tvalues calculated using each spin lock type are shown in Table 2. The mean Tvalues for normal tissue of block, HS_10, and HS_5 were 37.07 ms (range: 32.47–42.41 ms), 46.12 ms (range:

44.03–48.77 ms), and 49.99 ms (range: 47.97–51.43 ms), respectively.

Tvalues were significantly different between each spin lock type (Friedman test,Pb0.0001).

The Tvalues for each spin lock type are shown inFig. 8. The median Tvalues of normal liver function, Child–Pugh A, and Child–Pugh B or C were 37.00 ms, 40.77 ms, and 42.20 ms for block pulse; 46.75 ms, 50.78 ms, and 55.60 ms for HS8_10; and 48.80 ms, 55.42 ms, and 57.80 ms for HS8_5, respectively.

T values were not significantly different between normal liver function and Child–Pugh B or C using block pulse (Kruskal–Wallis, P= 0.038). We found a significant difference between normal liver function and Child–Pugh B or C using the HS8_10 pulse as well as the HS8_5 pulse, with a high significance level (Kruskal–Wallis,Pb0.01).

Fig. 4.Scheme of the amplitude and frequency modulation function for HS8_10 and HS8_5 locking of 20 ms duration. HS8_10 locking consists of two segments a) and HS8–5 consists of four segments b), with an MLEV-type phase cycle.

Fig. 5.Simulated longitudinal magnetization after each spin lock pulse at TSL 20 ms: a) block pulse, b) HS8_10, and c) HS8_5. Relative B1 amplitude is on the vertical axis, andΔB0 is on the horizontal axis, in kHz units. Thefinal longitudinal magnetization after locking with HS8_10 and HS8_5 is shown to be more homogeneous for a wide range of relative B1 amplitude and ΔB0 compared to using block pulses. The contour lines in the plot are per 0.2 Meq interval, with dark blue equal to–Meq and yellow equal to +Meq. (For interpretation of the references to colour in thisfigure legend, the reader is referred to the web version of this article.)

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4. Discussion

We investigated the effectiveness of applying a module consisting of stretched adiabatic pulses as a locking pulse to acquire robust Tmaps at 3 T. Using the block pulse, which is standard in most spin locking

sequences for whole body systems, we found severe artifacts on the source images. The use of adiabatic pulses reduces B1 inhomogeneity- related artifacts, which cause fatal errors in calculating Tvalues.

Witschey et al. reported a spin locking pulse that mitigates B0- and B1-type artifacts at allfield strengths[26]. This type of B0 and B1 Fig. 6.Source images for each TSL and the calculated Tmaps. The typical source images for each spin lock type are shown: block pulse (top), HS8_10 (middle), and HS8_5 (bottom) with the resulting Tmap (right). Using the block pulse, there are severe artifacts in segment 3 and segment 4 on each TSL image (white arrow) a), and severe artifacts in segment 7 and segment 8 on each TSL image (white arrow) b).

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insensitive spin lock pulse (90(x)–τ/2(y)–180(y)–τ/2(−y)–90(x)) was used for a neurological study. However, in our experience, it is not well suited for the liver due to the size of thefield of view of the liver compared to the brain and the heart.

The diagram of thefinal longitudinal magnetization simulated using the Bloch equations after presenting each type of spin lock pulse to the equilibrium magnetization clearly shows that the block pulse is very sensitive to B0 and B1 inhomogeneity (Fig.5). This will cause severe ar- tifacts on the image. In contrast, adiabatic spin locking results in a ho- mogeneousfinal magnetization for a wide range of B0 and B1fields. In particular, HS8_5 maintains homogeneity; therefore, it is useful for big organs, like the liver, where B0 and B1 are inhomogeneous, especially

at 3 T and higherfield strengths. However, there is no significant differ- ence in visual scoring between HS8_10 and HS8_5. Thus, we can con- clude that the HS8_10 is working as well as the HS8_5 within the range of B0 and B1 variations expected for a liver examination on a clin- ical 3 T system like the one we used. The difference in visual scoring be- tween the block and the two types of adiabatic spin locking pulse corroborates thefindings from the simulation. The stretched-type adia- batic spin locking pulse was able to provide homogeneous Timages.

Spin locking using adiabatic pulses represents a promising improve- ment to overcome B1 and B0 inhomogeneity, especially for body T imaging.

Both mean Tvalues obtained from the block and the two types of adiabatic spin locking pulse increased as liver function worsened. This result was similar to those previously reported[20,21,24]. However, the fundamental mechanisms leading to Tprolongation in liverfibro- sis and cirrhosis have not been fully investigated[24]. Wang et al.[20]

described the usefulness of Trelaxation for the evaluation of liverfi- brosis in a rat biliary duct ligation model. Takayama et al.[40]claimed that Trelaxation of the liver was not significantly correlated with liverfibrosis or with necro-inflammation. Thus, they concluded that Thas potential as a biomarker for the assessment of liver function, al- though it may not be suitable to estimate liverfibrosis or necro-inflam- mation. The present study did not investigate the mechanisms of T prolongation with liver dysfunction. Liver dysfunction may contribute to Tprolongation through combined mechanisms, such as biological, chemical, and physical factors, as Takayama et al. suggested.

The obtained Tvalues using the adiabatic pulses were longer than those using the block pulse, similar to the results obtained by Jokivarsi et al.[41]in normal rat brain parenchyma, even if the average Beffis equal, as for the HS8_10 pulse. We conjecture that this difference in Tis because the Beffof the adiabatic pulse is continuously changing during the pulse (Fig. 3), in contrast to the block pulse. The HS8_5 has a higher average Beff, therefore a different Tcan be expected[32,42].

Furthermore, temporal and spatial variation of Beffwill result in a vary- ing Trelaxation rate, which is difficult to control or predict. One must be aware of this when interpreting the Tvalues, and this should thus be done with extreme caution. Moreover, liver tissue contains a variety of macromolecules causing a mix of Tvalues within the voxels. Fur- ther, it is known that exchange and diffusion effects occur during Fig. 7.Results of visual scoring. The asterisk (*) represents a value ofPb0.001 between

block and HS8_5 and between block and HS8_10. There is no significant difference between HS8_10 and HS8_5 (P= 0.792).

Table 2

Difference in mean Tvalues and range for normal tissue between each spin lock type.

Spin lock pulse Block HS8_10 HS8_5

Mean T(ms) Range of T(ms) Standard deviation (ms)

37.07 32.47–42.41

±3.30

46.12 44.03–48.77

±1.78

49.99 47.97–51.43

±2.14

Pb0.0001.

Fig. 8.Comparison of Tvalues between block, HS8_10, and HS8_5. The graphs indicate mean liver Tvalues and standard deviation of Child–Pugh A, Child–Pugh B or C, and normal using each spin lock pulse. Each spin lock type is shown on the horizontal axis; Tvalues are on the vertical axis.

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locking and can affect thefinal signal. We did not study this aspect with- in the scope of this project.

It is thus difficult to achieve a meaningful absolute quantitative Tin the clinical setting because the Beffvaries temporally and spatially. How- ever, using adiabatic locking pulses provides a locking that is effective over a largefield of view and thus enables the calculation of homoge- neous Tmaps. The visual scores of the Tmaps acquired with adia- batic pulse locking are indeed higher compared to traditional block pulse locking. The visual scores for the respective Child–Pugh grades were not significantly different between HS8_10 and HS8_5. Further- more, the use of HS8_10 and HS8_5 pulses allows to differentiate be- tween normal and Child–Pugh B or C with high statistical significance.

There is a limitation in the present study. The pulse duration of the adiabatic pulse was determined by the modulation function and opti- mal adiabatic condition. The total locking pulse is limited to an even number of adiabatic pulse segments (Fig. 4), and thus the TSL duration was restricted to an even multiple of that segment duration. In this study, HS8_10 uses 10 ms per adiabatic pulse segment, and the TSLs were set to 20 ms and 40 ms. However, we believe that this restriction to the TSLs was not disadvantageous for the calculation of the T value of the liver, as mentioned in previous research[20,21,24].

In conclusion, we demonstrated that the stretched-type adiabatic spin locking method provides homogeneous and reduced artifact T liver images and is useful for a robust evaluation of liver function using T.

Disclosure of conflicts of interest

The authors have a conflict of interest to declare. Tomoyuki Okuaki and Marc Van Cauteren are Philips Healthcare employee. Tetsuo Ogino and Makoto Obara are Philips Electronics Japan employee. Yukihisa Takayama, Akihiro Nishie, Hiroshi Honda and Toshiaki Miyati have no relevant conflicts of interest to disclose.

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